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P 644. Diagnosis of Muscle–Eye–Brain Disease through Characteristic Neuroradiological Findings
30 October 2018 (online)
Background: Muscle–eye–brain disease MEB is a rare autosomal recessive congenital muscular dystrophy (CMD) characterized by an abnormal glycosylation of α-dystroglycan. The so-called α-dystroglycanopathies manifest with a marked clinical, biochemical, and genetical heterogeneity. Typical symptoms are early-onset muscular hypotonia with variable structural brain and eye anomalies. We present a patient with typical radiological findings which allowed us for an early genetic diagnosis and confirmation of the diagnosis MEB.
Case Report: The patient presented is a 3-month-old male infant born at term. Prenatal ultrasound showed asymmetric cerebral ventricles and suspected agenesis of the corpus callosum. After birth additional eye anomalies with persistent hyperplastic primary vitreous (PHPV) and microphthalmus on the left side became obvious. Clinically, the patient had feeding problems and at this time, mild signs of muscular hypotonia and development delay. The initial serum creatine kinase was normal.
Results: The cranial magnetic resonance imaging (MRI) confirms agenesis of the splenium of the corpus callosum and a triventricular hydrocephalus. In addition, there is ubiquitous polymicrogyria supra- and infratentorially, T2-alterations of white matter, multiple small cerebellar cysts, and hypoplastic brain stem with kinking. Both optic nerves are slim and PHPV on the left side is verified. Molecular genetic testing revealed two compound heterozygous variants in the POMGNT1 gene. One variant was previously described as pathogenic, and the other variant is predicted to be probably pathogenic. Thereby, the suspected diagnosis of MEB is confirmed.
Conclusion: In particular, the cerebellar cysts, the pons hypoplasia, and the kinking of the brain stem are characteristic neuroradiological findings of α-dystroglycanopathies with only a few differential diagnoses. Together with typical clinical symptoms and additional radiological findings, the diagnosis of MEB should be strongly considered. Typical but variable findings in MRI are a combination of neuronal migration disorder (polymicrogyria, alterations of white matter) and malformations of central nervous system (agenesis of corpus callosum, hydrocephalus). The cerebellar cysts cannot be detected prenatal and are not seen in all patients. MEB present with a triad of symptoms: muscular dystrophy with elevated creatine kinase and progressive muscular hypotonia, ocular anomalies often with functional blindness, and delayed psychomotor development. Creatine kinase can be normal in the first week of life and was elevated at our patient later on.
In addition to POMGTN1, there are 18 known genes causing α-dystroglycanopathies, all of them are involved in glycosylation of α-dystroglycan. Correct glycosylation of α-dystroglycan is a prerequisite for binding of ligands such as laminin. Thereby, α-dystroglycanopathies cause dysfunction of the cell membrane and cytoskeleton with symptoms of muscular dystrophy and disruption of neuronal migration. As a result of pronounced genotype–phenotype variability, a molecular genetic testing to confirm the diagnosis is necessary.